Naphthyridinomycin is a metabolite produced by a strain of Streptomyces. This compound was shown to have an unusual and complex heterocyclic structure. Some simple semisynthetic derivatives of naphthyridinomycin have been found to have significant inhibitory activity against the P-388 lymphoid leukemia system in mice. A strategy for total syntheses of naphthyridinomycin has been proposed which should allow for an efficient stereoselective preparation of this metabolite. It is hoped that this work will also provide some unnatural analogs of naphthyridinomycin for testing as anticancer agents by NCI.